Mitochondrial involvement in psychiatric disorders

Abstract

Recent findings of mitochondrial abnormalities in brains from subjects with neurological disorders have led to a renewed search for mitochondrial abnormalities in psychiatric disorders. A growing body of evidence suggests that there is mitochondrial dysfunction in schizophrenia, bipolar disorder, and major depressive disorder, including evidence from electron microscopy, imaging, gene expression, genotyping, and sequencing studies. Specific evidence of dysfunction such as increased common deletion and decreased gene expression in mitochondria in psychiatric illnesses suggests that direct examination of mitochondrial DNA from postmortem brain cells may provide further details of mitochondrial alterations in psychiatric disorders.

Figure 1

Diagram adapted from Lee et al. (106) showing five complexes involved in oxidative phosphorylation. We found decreased expression in brain for key mitochondrial DNA-encoded transcripts in neuropsychiatric disorders as shown in Table II.

Figure 2

The mitochondrial common deletion is increased in psychiatric disorders. The individual subjects are plotted by age and common deletion (x-axis ratio of 350/5000 bp). Subjects with BPD died at a younger age in this study; there was a significant increase in common deletion after age adjustment. The blue circle indicates the 95% confidence limits around the control subjects. The increase in the common deletion for nine psychiatric subjects is shown outside of the blue circle. Group abbreviations are shown in Table I.

Figure 3

Genotyping for large common deletion. Subjects were genotyped in duplicate at two concentrations. Arrows indicate presence of deletion relative to 5000 bp upper non-deleted band. Group abbreviations are shown in Table I.